rs864321672
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015100.4(POGZ):c.2763_2764insC(p.Thr922HisfsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
POGZ
NM_015100.4 frameshift
NM_015100.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -2.57
Genes affected
POGZ (HGNC:18801): (pogo transposable element derived with ZNF domain) The protein encoded by this gene appears to be a zinc finger protein containing a transposase domain at the C-terminus. This protein was found to interact with the transcription factor SP1 in a yeast two-hybrid system. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 50 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-151406271-T-TG is Pathogenic according to our data. Variant chr1-151406271-T-TG is described in ClinVar as [Pathogenic]. Clinvar id is 218147.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POGZ | NM_015100.4 | c.2763_2764insC | p.Thr922HisfsTer22 | frameshift_variant | 19/19 | ENST00000271715.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POGZ | ENST00000271715.7 | c.2763_2764insC | p.Thr922HisfsTer22 | frameshift_variant | 19/19 | 1 | NM_015100.4 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 06, 2016 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Nov 10, 2015 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jul 25, 2017 | The c.2763dupC variant in the POGZ gene has been reported previously as de novo in an individual with developmental delay, behavior problems, microcephaly, hearing loss, short stature, congenital malformations, cortical blindness, and dysmorphic features (White et al., 2016). The c.2763dupC variant causes a frameshift starting with codon Threonine 922, changes this amino acid to a Histidine residue, and creates a premature Stop codon at position 22 of the new reading frame, denoted p.Thr922HisfsX22. This variant is predicted to cause loss of normal protein function through protein truncation as the last 489 amino acids are lost and replaced by 21 incorrect amino acids. The c.2763dupC variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.2763dupC as a pathogenic variant. - |
Computational scores
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Calibrated prediction
Score
Prediction
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at